DNA甲基化与胃癌关系的研究进展
Research Progress on the Relationship between DNA Methylation and Gastric Cancer
DOI: 10.12677/ACM.2021.113139, PDF,    科研立项经费支持
作者: 孙良旭*：山东第一医科大学(山东省医学科学院)，山东 济南；山东省临沂市人民医院，山东 临沂；郭安兵, 张艳青, 彭利军#：山东省临沂市人民医院，山东 临沂
关键词: DNA甲基化；胃癌；表观遗传学；DNA甲基转移酶；DNA Methylation； Gastric Cancer； Epigenetics； DNA Methyltransferase
摘要: 胃癌是最常见的恶性肿瘤之一。我国胃癌发病率与死亡率依然较高，而很多胃癌患者初次发现时便已处于进展期，情况不容乐观，故对胃癌发生发展相关机制的深入研究并早日攻克胃癌显得尤为迫切。胃癌发病机制目前还没有完全清楚，目前主要认为是环境与饮食、感染、遗传与表观遗传协同作用导致，而DNA甲基化为表观遗传学中重要机制之一，近年来逐渐成为热点。DNA甲基化与胃癌的发生发展关系密切。DNA甲基化在胃癌发病过程中所起作用以及临床应用深入探索可能会对未来攻克胃癌产生深远意义。文章主要对近年来关于DNA甲基化与胃癌致病机制以及临床应用方面相关研究作出综述。
Abstract: Gastric cancer is one of the most common malignant tumors. The incidence and mortality of gastric cancer in my country are still high, and many patients with gastric cancer are already in the advanced stage when they are first discovered. The situation is not optimistic. Therefore, it is particularly urgent to study the related mechanisms of gastric cancer occurrence and development as soon as possible. The pathogenesis of gastric cancer is not yet fully understood. At present, it is mainly considered to be caused by the synergy of environment and diet, infection, genetics and epigenetics. DNA methylation is one of the important mechanisms in epigenetics and has gradually become a hot spot in recent years. DNA methylation is closely related to the occurrence and development of gastric cancer. The role of DNA methylation in the pathogenesis of gastric cancer and the in-depth exploration of its clinical application may have far-reaching significance in the future to overcome gastric cancer. This article mainly summarizes the research on DNA methylation and gastric cancer pathogenesis and clinical application in recent years.
文章引用：孙良旭, 郭安兵, 张艳青, 彭利军. DNA甲基化与胃癌关系的研究进展[J]. 临床医学进展, 2021, 11(3): 965-973. https://doi.org/10.12677/ACM.2021.113139

参考文献

[1] Bray, F., Ferlay, J., Soerjomataram, I., et al. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. [Google Scholar] [CrossRef] [PubMed]
[2] Rodriguez-Paredes, M. and Esteller, M. (2011) Cancer Epigenetics Reaches Mainstream Oncology. Nature Medicine, 17, 330-339. [Google Scholar] [CrossRef] [PubMed]
[3] Jin, Z. and Liu, Y. (2018) DNA Methylation in Human Diseases. Genes and Diseases, 5, 1-8. [Google Scholar] [CrossRef] [PubMed]
[4] Hu, X.T. and He, C. (2013) Recent Progress in the Study of Methylated Tumor Suppressor Genes in Gastric Cancer. Chinese Journal of Cancer, 32, 31-41. [Google Scholar] [CrossRef] [PubMed]
[5] Wang, K., Liang, Q., Li, X., et al. (2016) MDGA2 Is a Novel Tumour Suppressor Cooperating with DMAP1 in Gastric Cancer and Is Associated with Disease Outcome. Gut, 65, 1619-1631. [Google Scholar] [CrossRef] [PubMed]
[6] Ehrlich, M. and Lacey, M. (2013) DNA Hypomethylation and Hemimethylation in Cancer. Advances in Experimental Medicine and Biology, 754, 31-56. [Google Scholar] [CrossRef] [PubMed]
[7] Gaudet, F., Hodgson, J.G., Eden, A., et al. (2003) Induction of Tumors in Mice by Genomic Hypomethylation. Science, 300, 489-492. [Google Scholar] [CrossRef] [PubMed]
[8] Leodolter, A., Alonso, S., Gonzalez, B., et al. (2015) Somatic DNA Hypomethylation in H. pylori-Associated High-Risk Gastritis and Gastric Cancer: Enhanced Somatic Hypomethylation Associates with Advanced Stage Cancer. Clinical and Translational Gastroenterology, 6, e85. [Google Scholar] [CrossRef] [PubMed]
[9] Yang, J., Wei, X., Wu, Q., et al. (2011) Clinical Significance of the Expression of DNA Methyltransferase Proteins in Gastric Cancer. Molecular Medicine Reports, 4, 1139-1143.
[10] Yang, X.X., He, X.Q., Li, F.X., et al. (2012) Risk-Association of DNA Methyltransferases Polymorphisms with Gastric Cancer in the Southern Chinese Population. International Journal of Molecular Sciences, 13, 8364-8378. [Google Scholar] [CrossRef] [PubMed]
[11] Jurkowska, R.Z., Jurkowski, T.P. and Jeltsch, A. (2011) Structure and Function of Mammalian DNA Methyltransferases. Chembiochem, 12, 206-222. [Google Scholar] [CrossRef] [PubMed]
[12] Jobe, E.M., Gao, Y., Eisinger, B.E., et al. (2017) Methyl-CpG-Binding Protein MBD1 Regulates Neuronal Lineage Commitment through Maintaining Adult Neural Stem Cell Identity. Journal of Neuroscience, 37, 523-536. [Google Scholar] [CrossRef] 
[13] Wu, Y.C., Lv, P., Han, J., et al. (2014) Enhanced Serum Methylated p16 DNAs Is Associated with the Progression of Gastric Cancer. International Journal of Clinical and Experimental Pathology, 7, 1553-1562.
[14] 白艳丽, 金建军, 刘献民, 等. 胃癌p16基因启动子区甲基化状态的研究[J]. 中国实用医药, 2016, 11(14): 56-57.
[15] Peng, D., Zhang, H. and Sun, G. (2014) The Relationship between P16 Gene Promoter Methylation and Gastric Cancer: A Meta-Analysis Based on Chinese Patients. Journal of Cancer Research and Therapeutics, 10, 292-295. [Google Scholar] [CrossRef] [PubMed]
[16] Lim, H.K., Park, J.M., Chi, K.C., et al. (2013) Disappearance of Serum Methylated p16 Indicates Longer Survival in Patients with Gastric Cancer. Journal of Gastric Cancer, 13, 157-163. [Google Scholar] [CrossRef] [PubMed]
[17] Wen, J., Zheng, T., Hu, K., et al. (2017) Promoter Methylation of Tumor-Related Genes as a Potential Biomarker Using Blood Samples for Gastric Cancer Detection. Oncotarget, 8, 77783-77793. [Google Scholar] [CrossRef] [PubMed]
[18] Sakakura, C., Hamada, T., Miyagawa, K., et al. (2009) Quantitative Analysis of Tumor-Derived Methylated RUNX3 Sequences in the Serum of Gastric Cancer Patients. Anticancer Research, 29, 2619-2625.
[19] Yi, K.D., Kyoon, J.J., Kyu, P.Y., et al. (2007) E-Cadherin Expression in Early Gastric Carcinoma and Correlation with Lymph Node Metastasis. Journal of Surgical Oncology, 96, 429-435. [Google Scholar] [CrossRef] [PubMed]
[20] Yu, Q.M., Wang, X.B., Luo, J., et al. (2012) CDH1 Methylation in Preoperative Peritoneal Washes Is an Independent Prognostic Factor for Gastric Cancer. Journal of Surgical Oncology, 106, 765-771. [Google Scholar] [CrossRef] [PubMed]
[21] Shen, S., Chen, X., Li, H., et al. (2018) MLH1 Promoter Methylation and Prediction/Prognosis of Gastric Cancer: A Systematic Review and Meta and Bioinformatic Analysis. Journal of Cancer, 9, 1932-1942. [Google Scholar] [CrossRef] [PubMed]
[22] Li, Y., Yang, Y., Lu, Y., et al. (2015) Predictive Value of CHFR and MLH1 Methylation in Human Gastric Cancer. Gastric Cancer, 18, 280-287. [Google Scholar] [CrossRef] [PubMed]
[23] Shigeyasu, K., Nagasaka, T., Mori, Y., et al. (2015) Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer. PLoS ONE, 10, e130409. [Google Scholar] [CrossRef] [PubMed]
[24] 蒋伟, 张健锋, 毛振彪. 胃癌组织及外周血中CDX2基因甲基化的关系及其临床意义[J]. 交通医学, 2015, 29(4): 329-332.
[25] Liu, L. and Yang, X. (2015) Implication of Reprimo and hMLH1 Gene Methylation in Early Diagnosis of Gastric Carcinoma. International Journal of Clinical and Experimental Pathology, 8, 14977-14982.
[26] Pimson, C., Ekalaksananan, T., Pientong, C., et al. (2016) Aberrant Methylation of PCDH10 and RASSF1A Genes in Blood Samples for Non-Invasive Diagnosis and Prognostic Assessment of Gastric Cancer. PeerJ, 4, e2112. [Google Scholar] [CrossRef] [PubMed]
[27] Wang, G., Zhang, W., Zhou, B., et al. (2015) The Diagnosis Value of Promoter Methylation of UCHL1 in the Serum for Progression of Gastric Cancer. BioMed Research International, 2015, Article ID: 741030. [Google Scholar] [CrossRef] [PubMed]
[28] Hu, W., Zheng, W., Liu, Q., et al. (2017) Diagnostic Accuracy of DNA Methylation in Detection of Gastric Cancer: A Meta-Analysis. Oncotarget, 8, 113142-113152. [Google Scholar] [CrossRef] [PubMed]
[29] Lin, Z., Luo, M., Chen, X., et al. (2017) Combined Detection of Plasma ZIC1, HOXD10 and RUNX3 Methylation Is a Promising Strategy for Early Detection of Gastric Cancer and Precancerous Lesions. Journal of Cancer, 8, 1038-1044. [Google Scholar] [CrossRef] [PubMed]
[30] Wang, Y.B. and Ba, C.F. (2012) Promoter Methylation of Esophageal Cancer-Related Gene 4 in Gastric Cancer Tissue and Its Clinical Significance. Hepatogastroenterology, 59, 1696-1698.
[31] Pirini, F., Noazin, S., Jahuira-Arias, M.H., et al. (2017) Early Detection of Gastric Cancer Using Global, Genome-Wide and IRF4, ELMO1, CLIP4 and MSC DNA Methylation in Endoscopic Biopsies. Oncotarget, 8, 38501-38516. [Google Scholar] [CrossRef] [PubMed]
[32] Oishi, Y., Watanabe, Y., Yoshida, Y., et al. (2012) Hypermethylation of Sox17 Gene Is Useful as a Molecular Diagnostic Application in Early Gastric Cancer. Tumor Biology, 33, 383-393. [Google Scholar] [CrossRef] [PubMed]
[33] Baylin, S.B. (2005) DNA Methylation and Gene Silencing in Cancer. Nature Clinical Practice Oncology, 2, S4-S11. [Google Scholar] [CrossRef] [PubMed]
[34] Piekarz, R.L. and Bates, S.E. (2009) Epigenetic Modifiers: Basic Understanding and Clinical Development. Clinical Cancer Research, 15, 3918-3926. [Google Scholar] [CrossRef] 
[35] Deng, P., Chang, X.J., Gao, Z.M., et al. (2018) Downregulation and DNA Methylation of ECRG4 in Gastric Cancer. OncoTargets and Therapy, 11, 4019-4028. [Google Scholar] [CrossRef] 
[36] Yang, F., He, K., Huang, L., et al. (2017) Casticin Inhibits the Activity of Transcription Factor Sp1 and the Methylation of RECK in MGC803 Gastric Cancer Cells. Experimental and Therapeutic Medicine, 13, 745-750. [Google Scholar] [CrossRef] [PubMed]
[37] Wu, F.L., Li, R.T., Yang, M., et al. (2015) Gelatinases-Stimuli Nanoparticles Encapsulating 5-Fluorouridine and 5-Aza-2’-deoxycytidine Enhance the Sensitivity of Gastric Cancer Cells to Chemical Therapeutics. Cancer Letters, 363, 7-16. [Google Scholar] [CrossRef] [PubMed]
[38] Sugita, H., Iida, S., Inokuchi, M., et al. (2011) Methylation of BNIP3 and DAPK Indicates Lower Response to Chemotherapy and Poor Prognosis in Gastric Cancer. Oncology Reports, 25, 513-518. [Google Scholar] [CrossRef] [PubMed]
[39] Joo, J.K., Kim, S.H., Kim, H.G., et al. (2010) CpG Methylation of Transcription Factor 4 in Gastric Carcinoma. Annals of Surgical Oncology, 17, 3344-3353. [Google Scholar] [CrossRef] [PubMed]
[40] Oh, J.H., Jung, S.H., Hong, S.J., et al. (2015) DNA Methylation as Surrogate Marker for Gastric Cancer. Journal of Cancer Prevention, 20, 172-178. [Google Scholar] [CrossRef] 
[41] Yang, W., Mok, M.T., Li, M.S., et al. (2016) Epigenetic Silencing of GDF1 Disrupts SMAD Signaling to Reinforce Gastric Cancer Development. Oncogene, 35, 2133-2144. [Google Scholar] [CrossRef] [PubMed]
[42] Yuan, R., Wang, G., Xu, Z., et al. (2016) Up-Regulated Circulating miR-106a by DNA Methylation Promised a Potential Diagnostic and Prognostic Marker for Gastric Cancer. Anti-Cancer Agents in Medicinal Chemistry, 16, 1093-1100. [Google Scholar] [CrossRef] [PubMed]
[43] Shigaki, H., Baba, Y., Watanabe, M., et al. (2013) LINE-1 Hypomethylation in Gastric Cancer, Detected by Bisulfite Pyrosequencing, Is Associated with Poor Prognosis. Gastric Cancer, 16, 480-487. [Google Scholar] [CrossRef] [PubMed]
[44] Hu, C., Zhou, Y., Liu, C., et al. (2018) A Novel Scoring System for Gastric Cancer Risk Assessment Based on the Expression of Three CLIP4 DNA Methylation-Associated Genes. International Journal of Oncology, 53, 633-643. [Google Scholar] [CrossRef] [PubMed]
[45] Xu, X., Chang, X., Li, Z., et al. (2015) Aberrant SOX11 Promoter Methylation Is Associated with Poor Prognosis in Gastric Cancer. Cellular Oncology, 38, 183-194. [Google Scholar] [CrossRef] [PubMed]
[46] Sui, B.Q., Zhang, C.D., Liu, J.C., et al. (2018) HOXB13 Expression and Promoter Methylation as a Candidate Biomarker in Gastric Cancer. Oncology Letters, 15, 8833-8840. [Google Scholar] [CrossRef] [PubMed]
[47] Harada, H., Hosoda, K., Moriya, H., et al. (2019) Cancer-Specific Promoter DNA Methylation of Cysteine Dioxygenase Type 1 (CDO1) Gene as an Important Prognostic Biomarker of Gastric Cancer. PLoS ONE, 14, e214872. [Google Scholar] [CrossRef] [PubMed]
[48] Deng, J., Liang, H., Dong, Q., et al. (2014) The Survival Decrease in Gastric Cancer Is Associated with the Methylation of B-Cell CLL/Lymphoma 6 Member B Promoter. Open Biology, 4, Article ID: 140067. [Google Scholar] [CrossRef] [PubMed]
[49] Wu, L., Zhang, C., Wang, X., et al. (2016) Methylation of ASC/TMS1 Promoter Is Associated with Poor Prognosis of Patients with Gastric Cancer. Clinical and Translational Oncology, 18, 296-303. [Google Scholar] [CrossRef] [PubMed]
[50] Zhang, J., Dai, W. and Yang, X. (2015) Methylation Status of TRAF2 Is Associated with the Diagnosis and Prognosis of Gastric Cancer. International Journal of Clinical and Experimental Pathology, 8, 14228-14234.

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